Rat brain contains insulin-immunoreactive material and insulin binding sites. The insulin and binding site content shows regional distribution; it is high in the olfactory bulb. Using slices of the olfactory bulb we have found that insulin like dopamine (DA) can stimulate an accumulation of cAMP. Although DA and insulin enhance the cAMP content when given separately, they can no longer act when given together. Haloperidol, which can partially block the DA effect, is ineffective on insulin-dependent cAMP accumulation. Sulpiride, which fails to change the basal cAMP levels, curtails the cAMP accumulation elicited by insulin. Since internalization of insulin may be a mechanism that explain interactions between DA and insulin in olfactory bulb, we have studied insulin internalization using frog erythrocytes as a model system. Our results show that after 30 minutes of incubation at 30 degrees C about 80% of insulin is tenaciously bound to the cells and cannot be removed by procedures which detach the hormone bound to the cell surface, suggesting that insulin internalization has occurred. This tenacious linkage is temperature dependent and requires metabolic energy. Studies are in progress to elucidate the functional significance of this insulin internalization.